A new, chemically distinct antagonist at
dopamine 'D1-like' receptors, the thienoazepine
LY 270411, ([+]-2(3-chloro-6-methyl-8-phenyl-5,6,7,8 -tetrahydro-4H-thieno[2,3d]azepin-2-yl)propan-2-ol) was compared with the
isoquinoline BW 737C ([
S]-6-chloro-1-[2,5-dimethoxy-4- propylbenzyl]-7-hydroxy-2-methyl-1,2,3,4-
tetrahydroisoquinoline) and the benzazepine
SCH 23390 ([R]-7-chloro-8-hydroxy-2,3,4,5-tetrahydro-3-methyl-1-phenyl-1 H-3-benzazepine) for effects on behavioural responses to the isochroman full efficacy
dopamine 'D1-like' receptor agonist
A 68930 ([1R,3S]-1-aminomethyl-5, 6-dihydroxy-3-phenylisochroman) vs. the
dopamine 'D2-like' receptor agonist
RU 24213 (N-n-propyl-N-phenylethyl-p-3-hydroxyphenylethylamine). Grooming responses to
A 68930 were readily blocked by each of
LY 270411,
BW 737C and
SCH 23390; however, the vacuous chewing response was blocked only by
BW 737C. Sniffing and locomotor responses to
RU 24213 were attenuated by
BW 737C and
SCH 23390 but not by
LY 270411; furthermore,
myoclonic jerking to
RU 24213 was released by
BW 737C and
SCH 23390 but not by
LY 270411. These findings indicate that grooming induced by
dopamine 'D1-like' receptor agonism is blocked by all chemical classes of
dopamine 'D1-like' receptor antagonist while vacuous chewing is blocked only by
isoquinoline dopamine 'D1-like' receptor antagonism; this suggests that these behaviours may be mediated via functionally and pharmacologically distinct subtypes of
dopamine 'D1-like' receptor. Furthermore,
LY 270411 appears unique in its activity to readily block 'D1-like' receptor agonist-induced grooming without influencing behavioural responses to
dopamine 'D2-like' receptor agonism; thus, the site mediating prototypical
dopamine 'D1-like' receptor agonist-induced behaviours may be dissociable pharmacologically from
dopamine 'D1-like' site(s) participating in functional interactions with
dopamine 'D2-like' receptors.